• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Study on Pathophysiology, Prevention and Gene Therapy of Adrenoleukodystrophy

Research Project

Project/Area Number 10670718
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionGifu University

Principal Investigator

SUZUKI Yasuyuki  Gifu Univ. Pediatrics Associate Professor, 医学部, 助教授 (00163014)

Co-Investigator(Kenkyū-buntansha) SHIMOZAWA Nobuyuki  Gifu Univ. Pediatrics Assistant Professor, 医学部・附属病院, 講師 (00240797)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsAdrenoleukodystrophy / Peroxisome / Very long chain fatty acid / Bone marrow transplantation / Membrane protein / 極長錆脂肪酸 / 極長鎖脂肪酸活性化酵素 / ロレンゾ油
Research Abstract

Pathophysiology, prevention and treatment of X-linked adrenoleukodystrophy (ALD) were investigated.
1) Natural course of 15 Japanese patients with childhood and adrescent ALD was clarified. Average onset was 8.5 years of age. Though the most common first symptom was visual disturbance (n=7), mental deterioration rapidly progressed. The appearance of bed-ridden and dysphagia were significantly later than that of mental retardation.
2) The effects of BMT in Childhood ALD were described in four Japanese patients. Two elder patients with relatively maintained IQ levels had favorable results. Two younger patients with a rapid course and unmeasurable IQ levels at BMT showed deterioration of neurological functions.
3) The role of PMP70, a peroxisomal membrane protein which has a homology to ALD protein, was investigated. When PMP70 was expressed in CHO cells, the oxidation rate of palmitate was increased, however, the oxidation of lignocerate was decreased. PMP70 is involved in metabolic transport of long chain fatty acids and may form a heterodimer with ALD protein.
4) Genes and functions of several peroxisomal membrane protein were investigated. PEX13 was the pathogenic gene of peroxisomal biogenesis disorders group H. Gene structure and novel 11 mutations of PEX6 were identified in group C peroxisome biogenesis disorders. A point mutation G843D in PEX1 was the temperature-sensitivity causing mutation in group 1 peroxisome biogensis disorder.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Suzuki Y., et al.: "Bone marrow transplantation for the treatment of X-linked adrenoleukodystrophy"J. Inher. Metab. Dis.. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imanaka T., et al.: "Characterization of the 70-kDa peroxisomal membrane protein, an ATP binding cassette1 transporter. 1999"J. Biol. Chem.. 274. 11968-11976 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki, et al.: "Prenatal diagnosis of peroxisomal D-3-hydroxy-acyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency"J. Hum. GeneT. 44. 143-147 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimozawa N., et al.: "Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders"Hum. Mol. GeneT.. 8. 1077-1083 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhang,Z., et al.: "Genomic structure and identification of 11 novel mutations of the PEX6 gene in patients with peroxisome biogenesis disorders"Hum. Mutat.. 13. 487-496 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuzono Y., et al.: "Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomalmembrane assembly"Proc. Natl. Acad. Sci. USA. 96. 2116-2121 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 下澤伸行 ほか: "ペルオキシソーム欠損症の病態と遺伝子"小児科(金原出版). 9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 鈴木康之 ほか: "新しいペルオキシソーム病"脳と神経(医学書院). 8 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki Y, Isogai K, Teramoto T, et al.: "Bone marrow transplantation for the treatment of X-linked adrenoleukodystrophy."J Inher Metab Dis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imanaka T, Suzuki Y, Osumi T et al.: "Characterization of the 70-kDa peroxisomal membrane protein, an ATP binding cassette1 transporter."J Biol Chem. 274. 11968-11976 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki Y, Zhang Z, Shimozawa N, et al.: "Prenatal diagnosis of peroxisomal D-3-hydroxy-acyl-CoA dehydratase/ D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency."J Human Genet. 44. 143-147 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimozawa N, Suzuki Y, Zhang Z, et al.: "Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders."Hum Mol Genet. 8. 1077-1083 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhang Z, Suzuki Y, Shimozawa N, et al.: "Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders."Hum Mutat. 13. 487-496 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuzono Y, Suzuki Y, Fujiki Y et al.: "Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly."Proc Natl Acad Sci USA. 96. 2116-2121 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Grunsven Egv, Suzuki Y, Wander RJA et al.: "Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis."Am J Hum Genet. 64. 99-107 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honsho M, Suzuki Y, Fuhuki Y et al.: "Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D."Am J Hum Genet. 63. 1622-1630 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimozawa N, Suzuki Y, Zhang Z, et al.: "Genetic basis of peroxisome assembly mutants of humans, CHO cells and yeast: identification of a new complementation group of peroxisome biogenesis disorders, absent from peroxisomal membrane ghosts."Am J Hum Genet. 63. 1898-1903 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imamura A, Shimozawa N, Suzuki Y, et al.: "Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders in the highest-incidence group."Hum Mol Genet. 7. 2089-2094 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imamura A, Shimozawa N, Suzuki Y, et al.: "Temperature sensitive phenotypes of peroxisome assembly processes represent the milder forms of human peroxisome biogenesis disorders."Am J Hum Genet. 62. 1539-1543 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukuda S, Suzuki Y, Shimozawa N, et al.: "Amino acid and nucleotide sequences of human peroxisomal enoyl-CoA hydratase:3-hydroxyacyl-CoA dehydrogenase cDNA."J Inher Metab Dis. 21. 23-28 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki Y,et al.: "Bone marrow transplantation for the treatment of X-linked adrenoleukodystrophy."J Inher Metab Die. in press. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Imanaka T,Suzuki Y et al.: "Characterization of the 70-kDa peroxisomal membrane protein,an ATP binding cassette1 transporter.1999"J Biol Chem. 274. 11968-11976 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki Y,et al.: "Prenatal diagnosis of peroxisomal D-3-hydroxy-acyl-CoA dehydratase/D-3-hydroxyacy1-CoA dehydrogenase bifunctional protein deficiency."J Human Genet. 44. 143-147 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimozawa N,Suzuki Y,et al.: "Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders."Hum Mol Genet. 8. 1077-1083 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zhang Z,Suzuki Y, et al.: "Genomic structure and identification of 11 novel mutations of the PEX6 gene in patients with peroxisome biogenesis disorders ."Hum Mutat. 13. 487-496 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuzono Y,Suzuki Y,et al: "Human PEX19:cDNA cloning by functional complementation,mutation analysis in a patient with Zellweger syndrome,and potential role in peroxisomalmembrane assembly."Proc Natl Acad Scl USA. 96. 2116-2121 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 下澤伸行,鈴木康之他: "ペルオキシソーム欠損症の病態と遺伝子"小児科(金原出版). 9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木康之,下澤伸行他: "新しいペルオキシソーム病"脳と神経(医学書院). 8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Imamura A, Suzuki Y, et al: "Temperature sensitive phenotypes of peroxisome assembly processes represent the milder forms of human peroxisome biogenesis disorders." Am J Hum Genet. 62. 1539-1543 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Honsho M, Suzuki Y, et al: "Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D." Am J Hum Genet. 63. 1622-1630 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimozawa N, Suzuki Y, et al: "Genetic basis of peroxisome assembly mutants of humans, CHO cells and yeast" Am J Hum Genet. 63. 1898-1903 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Imamura A, Suzuki Y, et al: "Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders in the highest-incidence group." Hum Mol Genet. 7. 2089-2094 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Grunsven EGv, Suzuki Y, et al: "Peroxisomal bifunctional protein deficiency revisited : resolution of its true enzymatic and molecular basis." Am J Hum Genet. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki Y, Zhang Z, et al: "Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency." J Human Genet. (in press). (1999)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi